Simvastatin as an add-on Treatment to Copaxone for the Treatment of Relapsing Multiple Sclerosis

A Double Blind, Randomised, Placebo Controlled Study Investigating Simvastatin as an add-on Treatment to Copaxone for the Treatment of Relapsing Multiple Sclerosis in Patients Treated With Copaxone for at Least 3 Months

A Double Blind, Randomised, Placebo Controlled Study Investigating Simvastatin as an add-on Treatment to Copaxone for the Treatment of Relapsing Multiple Sclerosis in patients treated with Copaxone for at least 3 months

Study Overview

• Status: Withdrawn
• Conditions: Relapsing Remitting Multiple Sclerosis
• Intervention / Treatment: Drug: placebo; Drug: Simvastatin

Detailed Description

This is a double blind, placebo controlled, randomised, phase 3 study. Patients that have been treated with Copaxone for at least 6 months at the screening visit will be randomised for treatment with simvastatin or placebo as an add-on to their Copaxone treatment. Patients will start treatment with 40 mg peroral simvastatin daily (or an apparently identical placebo) for one month. Hereafter, patients will escalate dosage to 80 mg daily. The patients will be examined clinically at screening, baseline and at 3, 6 and 12 months. Blood samples for immunology will be performed at baseline and at 1, 3, 6 and 12 months. Blood samples for safety assessments will be performed at all study visits. MRI will be performed (T1-weighted and T2-weighted) at baseline and at 6 and 12 months.

• Study Type: Interventional
• Phase: Phase 3

Contacts and Locations

Study Locations

• Denmark
  • Glostrup, Denmark, 2600
    • Department of Neurology, Glostrup University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• A patient may be included if s/he fulfils all criteria mentioned below:

  • The patient must give written informed consent prior to any study related activities. Study related activities are any procedures that would not have been performed during normal management of the patient.
  • Is between the age of 18 and 60 years (both included).
  • Suffers from definite relapsing-remitting MS according to Poser criteria (CDMS or LSDMS) 21 or definite MS according to McDonald criteria 22.
  • Has a disability equivalent to an EDSS of 6.5 or less 20.
  • Has shown clinical activity defined as at least one reported or documented relapse within the last year or two reported or documented relapses within the last two years.
  • Has been treated with Copaxone for at least 3 months.
  • The patient must be prepared to and considered able to follow the protocol during the whole study period and to attend the planned visits, even if the treatment has to be withdrawn.

Exclusion Criteria:

• The patient must not be included if any of the criteria mentioned below are fulfilled:

  • Any condition that might give rise to similar symptoms as MS.
  • Has received treatment with glucocorticoids or ACTH later than one month prior to inclusion into the study, i.e. at the screening visit.
  • Has experienced the onset of a relapse within one month prior to inclusion into the study, i.e. at the screening visit.
  • Has suffered from major depression.
  • Has received immuno-suppressive treatment in the 6 months prior to screening.
  • Alcohol or drug dependency.
  • Has cardiac insufficiency, cardiomyopathy, significant cardiac dysrhythmia, unstable or advanced ischemic heart disease (NYHA III or IV).
  • Significant hypertension (BP > 180/110 mmHg).
  • Has renal insufficiency defined as serum creatinine > 1.5 times the upper normal reference limit.
  • ASAT and/or ALAT more than 1.5 times the normal upper reference limit.
  • Leucopaenia < 2.5 x 109/L or thrombopaenia < 100 x109/L.
  • Any medical illness requiring treatment with systemic corticosteroids.
  • Any systemic disease that can influence the patient's safety and compliance, or the evaluation of the disability.
  • Women who are pregnant, breast-feeding or have the possibility for pregnancy during the study. To avoid pregnancy, women have to be postmenopausal, surgically sterile, sexually inactive or practice reliable contraception (contraceptive pill, intrauterine device, administration of deposit of progestins, subcutaneous implants, contraception ring, transdermal deposit plaster).
  • Known or suspected allergy to study product or related products.
  • Participation in any other studies, involving other investigational product, within 30 days prior to participating in this study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: 2	Drug: placebo; calcium tablets once daily
Active Comparator: 1	Drug: Simvastatin; 80 mg once daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of new and/or enlarging lesions on T2- weighted MRI based on MRI done 12 months following baseline compared with MRI done at baseline.	one year

Secondary Outcome Measures

Outcome Measure	Time Frame
Changes in the EDSS score between baseline and 12 months after baseline.	one year
Changes in the MFSC score between baseline and 12 months after baseline.	one year
Number of documented relapses after baseline.	one year
Changes in immunological parameters	one year
Regulation of immunological activation.	one year

Collaborators and Investigators

• Sponsor: Anna Tsakiri
• Collaborators: Sanofi
• Investigators: Principal Investigator: Jette L Frederiksen, DMSC, Department of Neurology, Glostrup Hospital, Denmark

Study record dates

Study Major Dates

• Study Start: March 1, 2008
• Study Completion (Anticipated): March 1, 2011

Study Registration Dates

• First Submitted: January 30, 2007
• First Submitted That Met QC Criteria: January 30, 2007
• First Posted (Estimate): January 31, 2007

Study Record Updates

• Last Update Posted (Estimate): February 20, 2014
• Last Update Submitted That Met QC Criteria: February 19, 2014
• Last Verified: February 1, 2014

More Information

Terms related to this study

• Keywords: Simvastatin; Copaxone; CNS Inflammation
• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Autoimmune Diseases; Multiple Sclerosis; Sclerosis; Multiple Sclerosis, Relapsing-Remitting; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Simvastatin
• Other Study ID Numbers: CoSim-01; EudraCT number 2006-001827-21